The early years of the combination antiretroviral (ARV) therapy era have brought about dramatic reductions in morbidity and mortality associated with HIV infection in industrialized countries and, recently, international and local initiatives have allowed access to HAART in the developing world. Preliminary data from our prior work and others have shown that good adherence is feasible in resource-limited settings, but it is unclear whether these results are reproducible in scaled-up ART programs and what interventions would likely be effective at maximizing adherence in such settings. This proposal aims to address these important knowledge gaps by developing the infrastructure to conduct randomized trials of adherence interventions for populations affected by HIV/AIDS and poverty in sub-Saharan Africa. Specifically, we aim to: 1) determine the reliability of adherence measurement tools for assessing clinical adherence in poverty-affected Malawian HIV+ patients; 2) determine the impact of fixed-dose therapy on viral suppression, CD4 cell count decline, and development of resistance; and 3) determine barriers and facilitators to achieving excellent adherence, and examine potential interventions for evaluating in clinical trials, through qualitative methods. This study will generate critically important knowledge on the appropriate measurement of adherence in poverty-affected patients as well as provide strong inferences about culturally acceptable methods of improving adherence in this population. As our population is largely representative of HIV/AIDS populations in the region, we believe our results will be widely generalizable. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as it aims to determine the reliability of tools used to measure ART adherence in African patients. Our proposal further aims to address issues of cultural acceptability of interventions to be assessed in clinical trials.